Using the estrogen-induced and dependent renal adenocarcinoma of the hamster we plan to develop an autonomous kidney tumor from the endocrine-dependent tumor by serial transplantation. We have developed a cell culture system for growing renal adenocarcinoma cells in vitro and will use this to study the properties of these cells in vitro. We have found that hypophysectomized hamsters do not develop tumors even after 15 months of implantation with DES pellets. In intact animals the DES pellets typically induce hypertrophy of the pituitary and occasionally the pituitary becomes tumorous. We are planning to investigate the role of the pituitary and of pituitary hormones in permitting the renal adenocarcinomas to develop. We are comparing the sequence of events involved in the estrogen-induced stimulation of growth in a target tissue to the sequence of events in estrogen-induced tumorigenesis in the kidney. Our experiments to date to determine whether the proximal carcinogenic agent in this system is diethylstilbestrol itself or some metabolite has so far yielded no compelling evidence to suggest that tumorigenesis is caused by anything other than DES itself. We are investigating whether estrogen-induced tumorigenesis involves changes in the genetic mechanism which can be detected as alterations in the kinds of mRNA and proteins produced.